Inhibition of calcium signaling in ultraviolet-irradiated fibroblasts: role of tyrosine phosphorylation and protein kinase C.

Our aim was to study whether ultraviolet radiation produced any alterations in the subsequent signaling response of V79 fibroblasts to mitogenic stimulus. In ultraviolet C (UVC)-irradiated V79 fibroblasts, increase in cytosolic calcium in response to thrombin was nearly abolished in the presence of 3 mM external Ca(2+). UVC-treated V79 cells showed a greatly enhanced permeability to Ca(2+) which was reversed by pretreatment with genistein, a tyrosine kinase inhibitor. Genistein also alleviated the inhibition of thrombin response caused by UVC. In UVC-treated cells, significant activation of protein kinase C (PKC) occurred only on exposure to 3 mM external calcium and PKC inhibitors (H-7 or staurosporine) reversed UVC-induced adverse effects on the thrombin response. Therefore, it is likely that protein tyrosine phosphorylation by UVC may play a role in the subsequent inhibition of thrombin response in V79 cells through increased calcium influx and activation of PKC.